Silvia Morel

Emulsions containing partially water-miscible solvents for the preparation of drug nanosuspensions

The aim of this study was to investigate the feasibility of partially water-miscible solvents, such as benzyl alcohol, butyl lactate and triacetin, to prepare drug nanosuspensions by a solvent quenching technique. Mitotane, which possesses very poor water solubility and low bioavailability, was used as model drug. Preparation was by emulsifying an organic solution of the drug in an aqueous solution of a stabilising agent followed by rapid displacement of the solvent from the internal into the external phase, provoking solid particle formation. To verify the influence of emulsion droplet size on the drug particle size, 0.1 or 0.2% of different emulsifiers (Tween 80, caprylyl-capryl glucoside or lecithin) and different homogenisation conditions (Ultra Turrax or a high pressure homogenizer at 200 or 1000 bar for three cycles) were used. In general, emulsion droplet size decreased with high pressure homogenization and on increasing the number of cycles. The size of drug particles, obtained after adding water at a constant rate, was dependent on the droplet size in the emulsion. Drug particles of approximately 80 nm were obtained using butyl lactate, supporting the hypothesis that drug particle formation by the emulsification diffusion process involves generating regions of local supersaturation. Because of the increase in available surface area, the dissolution rate of diaultrafiltrated suspensions increased greatly compared to commercial product.

PREPARATION OF GRISEOFULVIN NANOPARTICLES FROM WATER-DILUTABLE MICROEMULSIONS

Nanoparticles of griseofulvin, a model drug with poor solubility and low bioavailability, were prepared from water dilutable microemulsions by the solvent diffusion technique. Solvent-in-water microemulsion formulations containing water, butyl lactate, lecithin, taurodeoxycholate sodium salt (TDC) or dipotassium glycyrrhizinate (KG), 1,2-propanediol or ethanol were used. The formation of macroscopically homogeneous, stable, fluid, optically transparent, isotropic solutions (microemulsions) was investigated by constructing pseudo-ternary phase diagrams. In the presence of TDC or KG, microemulsion systems that remained transparent on water dilution could be obtained. The displacement of butyl lactate, with an excess of water, from the internal phase of the microemulsions containing the drug into the external phase, lead to successful fabrication of drug nanosuspensions. Nanoparticle size was dependent on microemulsion composition: using KG, griseofulvin nanoparticles below 100 nm with low polydispersity and an increased dissolution rate were obtained.

Thymopentin in solid lipid nanoparticles

Abstract The pentapeptide thymopentin was englobed in solid lipid nanoparticles prepared from warm microemulsions following two different methods: from O/W microemulsion by forming the more lipophilic ion-pair with hexadecylphosphate, and from W/O/W microemulsion by dissolving the pentapeptide in the aqueous internal phase. The incorporation of the hydrophilic drug was 5.2% and 1.7% respectively; in both cases, the in vitro release of thymopentin from the solid lipid nanoparticles followed a pseudo-zero-order kinetics.

NMR relaxometric investigations of solid lipid nanoparticles (SLN) containing gadolinium(III) complexes

This work deals with the preparation and relaxometric investigations of solid lipid nanoparticles (SLN) containing [Gd-DTPA(H2O)]2- and [Gd-DOTA(H2O)]-. These paramagnetic chelates are commonly used as contrast agents (CA) for magnetic resonance imaging (MRI) owing to their ability to strongly increase the tissue water proton relaxation rate. The amount of gadolinium(III) (Gd(III)) complex included in the SLN has been evaluated and, on this basis, it has been found that the longitudinal relaxivity of these Gd(III) chelates apparently does not vary, at physiological pH, following their inclusion in SLN. We are unable to establish whether this is due to the free exchange of water from the inner compartment containing the Gd(III) chelate to the bulk water or whether the observed relaxation rate is essentially determined by a fraction of the complex which is close to the surface of the SLN in a region easily accessible to the bulk water. At acidic pH values, the relaxivity of the paramagnetic SLN containing the less thermodynamically and kinetically stable [Gd-DTPA(H2O)]2- markedly increases. This effect may be ascribed to an increased immobilization and/or to an enhanced hydration of the complex on SLN.

Preparation and evaluation in vitro of colloidal lipospheres containing pilocarpine as ion pair

Abstract Aqueous dispersions of solid lipospheres containing up to 7.5% pilocarpine as lipophilic ion pairs were submitted to a preliminary evaluation. The lipospheres (diameter 75–85 nm) consisted mainly of stearic acid and egg lecithin; pilocarpine base was incorporated as ion pair with mono-octylphosphate, monodecylphosphate and monohexade-cylphosphate. The following parameters were investigated: stability constants (β) and lipophilicity of the ion pairs, size, polydispersity and drug content of the lipospheres, pilocarpine release in vitro. The preparations might constitute a promising vehicle for sustained ocular delivery of pilocarpine.

Release of drugs from oil-water microemulsions

Abstract The release of five drugs with different lipophilicities from oil-water (o/w) microemulsions (isopropyl myristate as oil, 1-butanol as cosurfactant, aerosol-OT as surfactant and buffer, pH 7.0, as the aqueous phase) was studied by determining mass transfer constants of the drugs through a hydrophilic membrane separating the o/w microemulsions from the receiving aqueous phase. The initial mass transfer constants measured were linearly related to the partition coefficients (Pcos) of the drugs in the oil-cosurfactant-water mixtures. The Pcos values were used to approximate the drug concentration in the aqueous phase of the emulsion. The initial mass transfer constants of different drugs calculated on the basis of these concentrations were very similar to the mass transfer constants of the drugs obtained by permeation studies through the same membrane using an aqueous phase.

Incorporation in lipospheres of [d-Trp-6]LHRH

Abstract Lipospheres containing a hydrophilic drug, [ d -Trp-6]LHRH, were prepared using w/o/w microemulsion. Incorporation of the hydrophilic drug, [ d -Trp-6]LHRH, was considerable (about 90%). The in vitro release of the peptide from the lipospheres was observed for 8 h.

W/O/W Multiple Emulsions for Dermatological and Cosmetic Use, Obtained with Ethylene Oxide Free Emulsifiers

W/O/W multiple emulsions with ethylene oxide free emulsifiers, compatible with the skin, were prepared. They were fresh and easy to spread on the skin. The emulsion showed a shear thinning flux. Their multiplicity was confirmed with optical microscope analysis. FeSO4 and K3Fe(CN)6, when introduced separately in the inner and outer aqueous phases of the emulsions, did not give coloration, but when introduced together in the same aqueous phase, give a blue color due to their reaction. This experiment confirmed the multiplicity of these systems. The external aqueous phase of the emulsions was confirmed by Brilliant Blue up take from one of the multiple emulsions prepared higher than that from its W/O primary emulsion. The stability of the systems was confirmed by tests of breaking to centrifuge, of storage at 40°C and by freeze‐thaw cycles.

Resveratrol in solid lipid nanoparticles

This article investigates the possibility of producing solid lipid nanoparticles (SLN) as protective vehicle of resveratrol, an antioxidant characterized by a fast trans-cis isomerization. SLN aqueous dispersions were produced by hot melt homogenization technique and characterized. It was found that the presence of tetradecyl-γ-cyclodextrin in SLN formulation induced an improvement of nanoparticle characteristics. Moreover, a significant reduction in resveratrol photodegradation was noted when the molecule was entrapped in SLN which became more pronounced in the presence of tetradecyl-γ-cyclodextrin. A notable in vitro porcine skin accumulation and an increased antioxidative efficacy were observed by entrapping resveratrol in nanoparticles.

Synergistic action of vitamin C and amino acids on vitamin E in inhibition of the lipoperoxidation of linoleic acid in disperse systems

Abstract The synergistic effect of some amino acids ( l -tryptophan, l -cysteine, l -alanine and glycine), glutathione, n -butylamine and of vitamin C on the antioxidant effect of vitamin E on the lipoperoxidation of linoleic acid in sodium dodecylsulphate micellar solutions and oil in water emulsions was examined at pH 5.0 and 7.0. The antioxidant activity of vitamin E, measured by oxygen consumption, was similar in both emulsions and micellar solutions. The addition of vitamin C produced only a slight synergistic effect at pH 5.0 and none, or a prooxidative effect, at pH 7.0. The amino acids studied exerted a synergistic effect only at pH 5.0, and their effectiveness was partially related to their lipophilicity.